Einstein/Rwanda/DRC Consortium for Research in HIV/HPV Malignancies

爱因斯坦/卢旺达/刚果民主共和国 HIV/HPV 恶性肿瘤研究联盟

• 批准号: 10267222
• 负责人: Kathryn M. Anastos
• 金额: $ 36.25万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-21 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267222
• 关键词: 12 year old; 15 year old; Address; Adult; Africa; Africa South of the Sahara; Anogenital venereal warts; Antibodies; Antibody titer measurement; Anus; Birth; Blood; Cancer Burden; Cancer Etiology; Cervical; Cervical Cancer Screening; Cessation of life; Clinical Research; Colposcopy; Country; Data; Dose; Effectiveness; Enrollment; Enzyme-Linked Immunosorbent Assay; Future; Gardasil; General Population; Generations; Genotype; Goals; HIV; HIV Infections; HIV Seronegativity; HPV-High Risk; Health Planning; High Prevalence; High Risk Woman; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 11; Human papillomavirus 16; Human papillomavirus 18; Human papillomavirus 6; Immune response; Immunity; Immunization Programs; Immunocompetent; Impairment; Infection; Lateral; Locales; Long-Term Effects; Longitudinal Studies; Malignant Neoplasms; Malignant Vaginal Neoplasm; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Malignant neoplasm of penis; Malignant neoplasm of vulva; Measures; Medical; Medicine; Methods; Military Hospitals; Natural History; Observational Study; Oral; Outcome; Papillomavirus; Performance; Population; Population Study; Prevalence; Prevention strategy; Prospective Studies; Prospective cohort study; Public Health; Reporting; Research; Resolution; Resources; Risk; Risk Factors; Rwanda; Safety; Sampling; Schools; Secondary to; Sensitivity and Specificity; Specimen; Surrogate Endpoint; Target Populations; Testing; Universities; Vaccinated; Vaccination; Virus-like particle; Visit; Woman; World Health Organization; aged; antibody test; base; carcinogenicity; cervical cancer prevention; cervicovaginal; cervicovaginal microbiome; chronic infection; cohort; college; comparison group; cost; effectiveness study; elementary school; follow-up; girls; human study; immunogenicity; innovation; malignant oropharynx neoplasm; oral infection; point of care; point of care testing; programs; prophylactic; protective effect; rare cancer; response; serosurvey; sixth grade; vaccine effectiveness; validation studies; virtual; young adult; young man; young woman

Abstract: Cervical cancer is the 4th most common cancer and cause of cancer-related death in women globally; in many lower-resource settings, especially sub-Saharan Africa (SSA), it is the most common. Virtually all cervical cancer and precancer are caused by high-risk human papillomavirus (hrHPV). HPV16 causes ~55- 60% and HPV18 causes ~10-15% of cervical cancer while the remaining ~12 HPV types cause the remaining 25-30% of cervical cancer. hrHPV, predominately HPV16, also causes most anal, vulvar, vaginal, and penile cancers and a significant proportion of oropharyngeal cancers. Prophylactic HPV vaccines have been developed and have shown to be nearly 100% protective against incident infection and related abnormalities against the target HPV types in the general population. However, the evidence for the effectiveness of prophylactic HPV vaccines in women living with human immunodeficiency virus (HIV) (WLWH) is less clear. HIV infection increases the risk of cervical cancer due to an impaired immune response to HPV. In 2011, Rwanda, a high-burden cervical cancer country in East Africa that has an HIV prevalence in adult women of 3.3%, implemented a national HPV vaccination program with Gardasil®, which protects against HPV16 and HPV18, the two HPV types that cause ~70% of cervical cancer, and HPV6 and HPV11, the two types that cause ~90% of anogenital warts (HPV6/11/16/18). Their program has achieved >90% coverage of the target population, primarily girls aged 12 years, annually. The implementation of a highly successful HPV vaccination program and the high prevalence of HIV, in addition to the research and medical capacity that Albert Einstein College of Medicine (Einstein) has helped to build at the Rwanda Military Hospital (RMH) and University of Rwanda (UR), makes Rwanda the ideal locale to study the long-term effects of HPV vaccination in WLWH. To answer questions about HPV vaccine effectiveness and immunity in Rwanda WLWH, collaborators at Einstein, RMH, and UR will conduct an observational study of WLWH and HIV-negative (HIV[-]) women who did (birth cohorts 1997 and later) and WLWH did not receive HPV vaccination (birth cohorts before 1997). We will compare the cervical, anal, and oral prevalent and 6-month persistent HPV6/11/16/18 infections in 757 HPV-vaccinated WLWH to those in 757 unvaccinated WLWH. We will also compare the HPV immune response in 548 HPV-vaccinated WLWH to 548 HPV-vaccinated HIV[-] women and the impact of switching from 3 doses to 2 doses of Gardasil in 2015. We also will validate a low-cost, simple point-of-care test for HPV16 antibodies as method to verify/determine HPV vaccination status. Finally, we will investigate the risk factors, including the cervicovaginal microbiome, for HPV persistence in WLWH. Our (long-term) goal is to establish a cohort of WLWH in whom we can examine the long-term effectiveness of HPV vaccination in WLWH now and in the future. This contribution is significant as it will establish the population effectiveness of HPV vaccination in WLWH living in SSA, the women at the highest risk of cervical cancer, for which there is a dearth of evidence. The proposed research is innovative as it leverages and expands the local research and medical capacity in Rwanda to examine one of the critically unanswered questions about HPV vaccine effectiveness in the context of the World Health Organization call for the global control of cervical cancer.

抽象的： 宫颈癌是全球女性第四大癌症，是癌症相关的死亡原因。 许多较低的资源环境，尤其是撒哈拉以南非洲（SSA），这是最常见的。几乎全部 宫颈癌和预科剂是由高风险的人乳头瘤病毒（HRHPV）引起的。 HPV16导致〜55- 60％和HPV18导致约10-15％的宫颈癌，而其余的约12 HPV导致剩余 25-30％的宫颈癌。 HRHPV，主要是HPV16，也导致大多数肛门，外阴，阴道和阴茎 癌症和大量的口咽癌。预防性HPV疫苗已经 开发并已显示几乎100％受到免受事件感染和相关异常的保护 针对普通人群中的目标HPV类型。但是，证明有效性的证据 患有人类免疫缺陷病毒（HIV）（WLWH）女性的预防性HPV疫苗不太清楚。 HIV感染增加了由于对HPV的免疫响应受损而导致宫颈癌的风险。 2011年，卢旺达是东非一个高负担的宫颈癌国家，在 3.3％的成年女性通过Gardasil®实施了国家HPV疫苗接种计划，该计划可保护 针对HPV16和HPV18，这两种HPV类型可导致约70％的宫颈癌，以及HPV6和HPV11， 导致约90％的肛门疣的两种类型（HPV6/11/16/18）。他们的计划已达到90％ 目标人群的覆盖范围，每年12岁的小学女孩。实施高度 除研究和医学外，成功的HPV疫苗接种计划和HIV的高流行率 阿尔伯特·爱因斯坦医学院（爱因斯坦）帮助在卢旺达军事医院建立了能力 （RMH）和卢旺达大学（UR），使卢旺达成为研究HPV长期影响的理想场所 WLWH疫苗接种。 回答有关HPV疫苗有效性和免疫力的问题，合作者 在爱因斯坦，RMH和UR将对WLWH和HIV阴性（HIV [ - ]）妇女进行观察性研究 DID（1997年及以后的出生队列）和WLWH未接受HPV疫苗接种（1997年之前的出生队列）。我们 将比较757中的宫颈，肛门和口腔普遍存在以及6个月的持久性HPV6/11/16/18感染 HPV接种量为757个未接种的WLWH的WLWH。我们还将比较HPV免疫 548 HPV接种量的WLWH对548 HPV接种疫苗的HIV [ - ]妇女的反应和转换的影响 2015年，从3剂到2剂Gardasil。我们还将验证低成本，简单的护理测试 HPV16抗体作为验证/确定HPV疫苗接种状态的方法。最后，我们将调查风险 WLWH中HPV持久性的因素，包括宫颈阴道微生物组。我们的（长期）目标是 建立一群WLWH，我们可以在其中检查HPV疫苗接种的长期有效性 现在和将来。这种贡献很重要，因为它将确定 居住在SSA的WLWH中的HPV疫苗接种，患有宫颈癌风险最高的妇女 证据死亡。拟议的研究具有创新性，因为它利用并扩展了当地研究和 卢旺达的医疗能力检查有关HPV疫苗的批判性问题之一 世界卫生组织的有效性要求全球控制宫颈癌。